Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.

Tunable compensation of second and third order dispersion by non-uniformly strained chirped fibre Bragg grating

A novel fibre grating device is demonstrated with tuneable chromatic dispersion slope. The tuning range is 70 to 190 ps/nm and 0 to 25 ps/nm2 for the second and third order dispersion, respectively.

Efficient optimisation of per-channel pre-compensation in WDM 20-Gbit/s RZ-DPSK transmission in non-slope matched submarine links

We propose a computationally efficient method to the per-channel dispersion optimisation applied to 50 GHz-spaced N × 20-Gbit/s wavelength division multiplexing return-to-zero differential phase shift keying transmission in non-zero dispersion-shifted fibre based submarine systems. Crown Copyright © 2010.

Soliton transmission at 10 Gbit/s over 2022 km of standard fibre with dispersion compensation

We present experimental results of 10 Gbit/s, 20 ps soliton data transmission over standard fibre, dispersion compensated to 0.5 ps/nm/km. Acceptable Q values were measured to a distance of 2022 km.

Optical phase conjugation for dispersion and nonlinearity compensation in a 1600km, 42 Gb/s quasi-lossless system

We experimentally investigate a long-distance, high-bit-rate transmission system which combines optical-phase-conjugation with quasi-lossless amplification. Comparison with a conventional system configuration demonstrates the possibility of obtaining both dispersion compensation and improved nonlinear tolerance using proposed scheme.

Novel complex gratings with third-order group-delay variations for tunable pure dispersion slope compensation

We present a novel tunable dispersion compensator that can provide pure slope compensation. The approach uses two specially designed complex fiber Bragg gratings (FBGs) with reversely varied third-order group delay curves to generate the dispersion slope. The slope can be changed by adjusting the relative wavelength positions of the two FBGs. Several design examples of such complex gratings are presented and discussed. Experimentally, we achieve a dispersion slope tuning range of +/-650ps/nm2 with >0.9nm usable bandwidth.

Design of films for oral dosage formulations

A novel method for tablet coating was studied where a thin polymer film was cast (pre-formed film), dried and applied as a coating hence eliminating the need for using any solvent during the actual coating process. A pre-formed film is initially heating to a temperature where it becomes flexible, a vacuum is applied and the film is then pulled around the tablet. The proposed films (gelatine or cellulose-based) were characterised in terms of their dissolution, swelling, mechanical and thermal properties prior to using them in the novel coating process; selected films were then coated onto tablets containing paracetamol or ibuprofen and the effect of the film on the subsequent dissolution was evaluated. It was found that the pre-formed films could be designed to be fast dissolving and mechanically strong to withstand the stress from the coating process. Also metoclopramide was incorporated in a gelatine film-coating formulation which was then successfully coated on paracetamol-containing core. Gelatin-based films were found to be successful in the novel coating process therefore to be suitable as finished coatings for immediate release dosage forms. Orally disintegrating dosage forms have been identified as a favourable dosage form due to the following reasons: fast onset of drug release, easy to use, not painful and possible increase of amount absorbed to systemic circulation. Selected films formulated for coating studies were also successfully formulated to contain active ingredient suitable for orally disintegrating dosage form; cellulose-based naratriptan-films were studied as orally disintegrating dosage forms of where the effect of formulation on the film properties was studied. It was found that strength of the film can affect the dissolution of the film but it may be the inclusion of specific excipients in the formulation which affect the penetration of the drug through mucosa.

Direct current ripple compensation for multi-phase fault-tolerant machines

A second-harmonic direct current (DC) ripple compensation technique is presented for a multi-phase, fault-tolerant, permanent magnet machine. The analysis has been undertaken in a general manner for any pair of phases in operation with the remaining phases inactive. The compensation technique determines the required alternating currents in the machine to eliminate the second-harmonic DC-link current, while at the same time minimising the total rms current in the windings. An additional benefit of the compensation technique is a reduction in the magnitude of the electromagnetic torque ripple. Practical results are included from a 70 kW, five-phase generator system to validate the analysis and illustrate the performance of the compensation technique.

MAP detection for impairment compensation in coherent WDM systems

We propose a novel recursive-algorithm based maximum a posteriori probability (MAP) detector in spectrally-efficient coherent wavelength division multiplexing (CoWDM) systems, and investigate its performance in a 1-bit/s/Hz on-off keyed (OOK) system limited by optical-signal-to-noise ratio. The proposed method decodes each sub-channel using the signal levels not only of the particular sub-channel but also of its adjacent sub-channels, and therefore can effectively compensate deterministic inter-sub-channel crosstalk as well as inter-symbol interference arising from narrow-band filtering and chromatic dispersion (CD). Numerical simulation of a five-channel OOK-based CoWDM system with 10Gbit/s per channel using either direct or coherent detection shows that the MAP decoder can eliminate the need for phase control of each optical carrier (which is necessarily required in a conventional CoWDM system), and greatly relaxes the spectral design of the demultiplexing filter at the receiver. It also significantly improves back-to-back sensitivity and CD tolerance of the system.

Electronic dispersion compensation using full optical-field reconstruction in 10Gbit/s OOK based systems

We investigate the design of electronic dispersion compensation (EDC) using full optical-field reconstruction in 10Gbit/s on-off keyed transmission systems limited by optical signal-to-noise ratio (OSNR). By effectively suppressing the impairment due to low- frequency component amplification in phase reconstruction, properly designing the transmission system configuration to combat fiber nonlinearity, and successfully reducing the vulnerability to thermal noise, a 4.8dB OSNR margin can be achieved for 2160km single-mode fiber transmission without any optical dispersion compensation. We also investigate the performance sensitivity of the scheme to various system parameters, and propose a novel method to greatly enhance the tolerance to differential phase misalignment of the asymmetric Mach-Zehnder interferometer. This numerical study provides important design guidelines which will enable full optical-field EDC to become a cost-effective dispersion compensation solution for future transparent optical networks.

Compensation of intra-channel nonlinear fibre impairments using simplified digital back-propagation algorithm

We investigate a digital back-propagation simplification method to enable computationally-efficient digital nonlinearity compensation for a coherently-detected 112 Gb/s polarization multiplexed quadrature phase shifted keying transmission over a 1,600 km link (20x80km) with no inline compensation. Through numerical simulation, we report up to 80% reduction in required back-propagation steps to perform nonlinear compensation, in comparison to the standard back-propagation algorithm. This method takes into account the correlation between adjacent symbols at a given instant using a weighted-average approach, and optimization of the position of nonlinear compensator stage to enable practical digital back-propagation.

Nonlinearity compensation in multi-rate 28 Gbaud WDM systems employing optical and digital techniques under diverse link configurations

Digital back-propagation (DBP) has recently been proposed for the comprehensive compensation of channel nonlinearities in optical communication systems. While DBP is attractive for its flexibility and performance, it poses significant challenges in terms of computational complexity. Alternatively, phase conjugation or spectral inversion has previously been employed to mitigate nonlinear fibre impairments. Though spectral inversion is relatively straightforward to implement in optical or electrical domain, it requires precise positioning and symmetrised link power profile in order to avail the full benefit. In this paper, we directly compare ideal and low-precision single-channel DBP with single-channel spectral-inversion both with and without symmetry correction via dispersive chirping. We demonstrate that for all the dispersion maps studied, spectral inversion approaches the performance of ideal DBP with 40 steps per span and exceeds the performance of electronic dispersion compensation by ~3.5 dB in Q-factor, enabling up to 96% reduction in complexity in terms of required DBP stages, relative to low precision one step per span based DBP. For maps where quasi-phase matching is a significant issue, spectral inversion significantly outperforms ideal DBP by ~3 dB.